A number of biopharmaceutical companies have successfully taken hemoglobin-based oxygen carriers (HBOC) into phase I clinical trial. However, transfusions have been limited to low dosage levels due to observed hypertensive and vasoconstrictive effects at high dosage levels in pre- c1inical animal studies. This proposal deals with the current HBOC's failure to have an oxidant detoxification system similar to the one which is intrinsic to the red blood cells it intends to substitute. This research plan intends to modify a high- quality HBOC, which is currently in clinical trials, to demonstrate that stable nitroxide free radicals can be used to perform an oxidant detoxification function. If the research is successful, then the groundwork would established for a second generation red blood cell substitute which could successfully commercialized.